Activity-dependent synaptic plasticity is believed to be the cellular basis for learning and memory. However, the relationship between the synaptic modification induced by simple patterns of activity in reduced preparations and functional plasticity in the intact brain remains an open question. Our goal is to bridge the gap in our understanding of activity-dependent neural plasticity between these two levels. In spike-timing-dependent synaptic plasticity (STDP), the direction and magnitude of synaptic modification depends on the relative timing of the pre- and postsynaptic spikes on the order of tens of milliseconds. Theoretical studies have highlighted this form of plasticity as a powerful learning rule that endows neural circuits with increased computational capacity. However, most of the previous studies on STDP used simple spike patterns to induce synaptic modification. These experiments may not provide sufficient information for understanding how STDP operates in the intact brain, where activity evoked by sensory stimuli exhibit complex spatiotemporal patterns. In the proposed project, we will carry out a series of experiments in cortical slices to systematically delineate the rules governing synaptic modifications induced by complex patterns of activity. The proposal is divided into two parts, addressing the temporal and the spatial properties of STDP. Regarding the temporal properties, we have developed a simple phenomenological model to predict the effects of complex spike trains in synaptic modification. In Part 1 of the proposed project, we will extend the previous study and will address several issues concerning the temporal interactions among multiple spikes in synaptic modification. Regarding the spatial properties, our preliminary studies suggest that synaptic modification may depend on dendritic location. Since synapses at different locations may serve different functions in information processing, the effect of dendritic location on synaptic modification may have important functional implications. In Part 2 of the proposed project we will investigate the effects of dendritic location on STDP. The temporal complexity of neuronal spiking and the spatial complexity of synaptic connections pose important challenges for understanding functional plasticity in the central nervous system. The proposed studies will provide important information for understanding how synaptic modifications are induced by natural stimuli and how they affect the functions of neuronal circuits in vivo.